| Size | Price | Stock | Qty |
|---|---|---|---|
| 50mg |
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| 100mg |
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Purity: ≥98%
| Targets |
GNE-207 targets the bromodomain of CREB-binding protein (CBP), a histone acetyltransferase and transcriptional coactivator that plays a critical role in regulating gene expression. CBP and its closely related paralog p300 are epigenetic reader proteins that bind acetylated lysine residues on histone tails, facilitating the assembly of transcriptional complexes. GNE-207 binds selectively to the CBP bromodomain with an IC50 of 1 nM, potently blocking the interaction between CBP and acetylated histones. This inhibition disrupts CBP-mediated transcription of target genes including MYC, a key oncogenic driver in many cancers.
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| ln Vitro |
GNE-207 is an orally accessible, effective, and selective CBP bromodomain inhibitor that has an IC50 of 1 nM and a selectivity index of >2500-fold against BRD4 (1) (IC50, 3.1 μM) [1]. GNE-207 exhibits exceptional CBP efficacy in MV-4-11 cells, with an EC50 of 18 nM for MYC expression [1].
GNE-207 demonstrates potent in vitro activity against CBP with an IC50 of 1 nM and shows excellent selectivity over BRD4 (>2500-fold). In MV-4-11 leukemia cells, GNE-207 suppresses MYC expression with an EC50 of 18 nM. The compound also inhibits the proliferation of MYC-dependent cancer cell lines. Mechanistic studies confirm that GNE-207 displaces CBP from chromatin, reduces histone acetylation at CBP-regulated enhancers, and downregulates MYC and other CBP target genes. The compound's in vitro potency and selectivity make it a valuable tool for studying the role of CBP in transcriptional regulation and oncogenesis. |
| ln Vivo |
GNE-207 (5 mg/kg) has a respectable oral bioavailability and a moderate PK clearance [1].
In vivo, GNE-207 demonstrates efficacy in preclinical models of MYC-driven cancers. Oral administration of GNE-207 at doses such as 5 mg/kg suppresses tumor growth in xenograft models. Pharmacodynamic studies confirm target engagement and on-target effects, including reduced MYC expression and decreased proliferation in tumor tissues. The compound's oral bioavailability and favorable pharmacokinetic profile enable sustained target inhibition in vivo. GNE-207 has been used to validate CBP as a therapeutic target for cancers dependent on MYC overexpression. In vivo efficacy correlates with the degree of CBP bromodomain occupancy and MYC suppression. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for GNE-207 measure its affinity for the CBP bromodomain using biochemical techniques such as fluorescence polarization (FP), AlphaScreen, or time-resolved fluorescence resonance energy transfer (TR-FRET). These assays use a fluorescently labeled acetylated histone peptide as a tracer, and displacement by GNE-207 is measured to determine IC50 values. Selectivity is assessed by screening GNE-207 against a panel of bromodomain-containing proteins including BRD2, BRD3, BRD4, BRDT, and other BET family members. Surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC) may be used to measure direct binding affinity (Kd). The >2500-fold selectivity over BRD4 confirms the compound's high specificity for CBP.
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| Cell Assay |
In vitro cellular assays for GNE-207 are performed in cancer cell lines that are dependent on MYC expression, such as MV-4-11 leukemia cells. Cells are treated with escalating concentrations of GNE-207 for 24-72 hours, and MYC expression is measured by Western blot or qRT-PCR to determine EC50 values. Cell proliferation and viability are assessed using CellTiter-Glo, MTT, or colony formation assays. The effects of GNE-207 on CBP chromatin occupancy are evaluated by ChIP-seq or ChIP-qPCR. Global gene expression changes are assessed by RNA-seq to identify CBP-regulated transcriptional programs. Apoptosis is quantified by caspase-3/7 activity or Annexin V staining.
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| Animal Protocol |
In vivo animal studies with GNE-207 are conducted in mouse xenograft models of MYC-driven cancers. Tumor-bearing mice receive GNE-207 via oral gavage at doses such as 5 mg/kg, administered once or twice daily. Tumor growth is monitored by caliper measurement, and tumor tissues are collected at endpoint for pharmacodynamic analysis including MYC expression (Western blot, IHC), proliferation markers (Ki67), and apoptosis (cleaved caspase-3). Compound levels in plasma and tumor tissue are measured by LC-MS/MS for PK-PD correlation. Body weight, clinical signs, and organ weights are monitored for safety assessment.
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| ADME/Pharmacokinetics |
GNE-207 displays a favorable pharmacokinetic profile with moderate clearance and good oral bioavailability following administration. At a dose of 5 mg/kg, the compound achieves therapeutic plasma concentrations sufficient for sustained CBP inhibition. The compound's half-life, clearance, volume of distribution, and oral bioavailability have been characterized in preclinical species. GNE-207 shows good oral absorption and moderate plasma protein binding. Metabolism occurs primarily via hepatic cytochrome P450 enzymes. The favorable PK properties support once- or twice-daily dosing in preclinical efficacy studies.
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| Toxicity/Toxicokinetics |
Toxicological data for GNE-207 are primarily derived from preclinical efficacy studies in mouse models. At efficacious doses, the compound appears to be generally well-tolerated, with no severe adverse effects reported in published literature. However, comprehensive toxicology studies including genotoxicity, safety pharmacology, and repeated-dose toxicity in rodent and non-rodent species would be required for clinical development. As a CBP bromodomain inhibitor, potential on-target toxicities could include effects on normal hematopoietic cells, given the role of CBP in regulating gene expression in multiple cell types. CBP inhibition may also affect other CBP-dependent physiological processes.
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| References | |
| Additional Infomation |
GNE-207 is a potent, selective, and orally bioavailable inhibitor of the CBP bromodomain, with an IC50 of 1 nM and >2500-fold selectivity over BRD4. It suppresses MYC expression with an EC50 of 18 nM in MV-4-11 cells. The compound is used as a chemical probe to study CBP-mediated transcription and MYC-driven oncogenesis. It is in preclinical development; no regulatory approvals have been reported. GNE-207 represents a promising approach for targeting MYC-dependent cancers.
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| Molecular Formula |
C29H30N6O3
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|---|---|
| Molecular Weight |
510.586905956268
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| Exact Mass |
510.237
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| CAS # |
2158266-58-9
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| PubChem CID |
132186469
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| Appearance |
White to off-white solid powder
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| LogP |
2
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
38
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| Complexity |
852
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O1CCC(CC1)N1C2CCN(C(C)=O)CC=2C(C2C=CC=C3C=C(C4C=NC(C(NC)=O)=CC=4)N=CC=23)=N1
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| InChi Key |
MUJXZEDIWKGKQD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C29H30N6O3/c1-18(36)34-11-8-27-24(17-34)28(33-35(27)21-9-12-38-13-10-21)22-5-3-4-19-14-26(32-16-23(19)22)20-6-7-25(31-15-20)29(37)30-2/h3-7,14-16,21H,8-13,17H2,1-2H3,(H,30,37)
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| Chemical Name |
5-(8-(5-Acetyl-1-(tetrahydro-2H-pyran-4-yl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl)isoquinolin-3-yl)-N-methylpicolinamide
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| Synonyms |
GNE-207; GNE207; GNE 207
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~200 mg/mL (~391.70 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (9.79 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 5 mg/mL (9.79 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 5 mg/mL (9.79 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9585 mL | 9.7926 mL | 19.5852 mL | |
| 5 mM | 0.3917 mL | 1.9585 mL | 3.9170 mL | |
| 10 mM | 0.1959 mL | 0.9793 mL | 1.9585 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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